Posted in BNT162b2 mRNA vaccine, Resource

Systems vaccinology of the BNT162b2 mRNA vaccine in humans

Interferon responses were most evident after 1 day post BNT162b2 vaccination, especially after the second vaccination. Source from Arunachalam et al., Nature, 2021

The Pfizer-BioNTech vaccine, BNT162b2 has ~95% efficacy, but little is known about the host immune responses involved. In this study by Arunachalam et al., the authors examined the host immune responses to this mRNA vaccine.

Immune responses were examined in 56 volunteers, each receiving two doses of the vaccine. Neutralizing antibodies were increased after primary vaccination, which boosted significantly after the second vaccination. Spike-specific CD4 and CD8 responses were more evident only after the second vaccination. No significant correlation were seen between T-cell, neutralizing antibodies and age were noted.

Phosphorylation of STAT1 and STAT3 in B-cells, T-cells, monocytes and pDCs were seen after 1 day post-vaccination, and especially after second vaccination. This observation was correlated with an induction of IFN-gamma and CXCL-10 protein expression at 1-2 days post-vaccination. Similarly, the induction of these cytokines was greater after second vaccination.

Consistent with the results from protein analysis, the transcriptional responses was greater after the second vaccination compared to the first vaccination (See top figure). Most of these responses were related to monocyte and inflammatory modules.

Single-cell transcriptomics reveal that the interferon signatures were broadly induced across cell types, much of which are driven by monocytes and dendritic cells. NK cell activation was only apparent at 1 day post second vaccination, which then disappears on the second day.

Comparing transcriptomics responses with other vaccines, the mRNA vaccine responses behave most similarly to the adjuvanted vaccines and live-viral vectors at day 1 post-vaccination. However, the authors did not detect any B-cell signatures in any of their time-points tested, despite seeing a significant increase in plasmablasts. Instead, the pathways related to interferon and inflammation were most correlated with neutralizing antibody and CD8 T-cell responses.